Optically-active amino acids in high purity are becoming increasingly important as intermediates for the preparation of pharmaceuticals, food and agrochemicals. For example, some are side chain precursors for the semisynthetic penicillins, ampicillin and amoxycillin. Also, the most important building block for the low calorie sweetener, aspartame, is L-phenylalanine. D-valine, for instance, is an intermediate for the pyrethroid insecticide, Fluvalinate. In addition, D-phenylalanine possesses analgesic properties and might one day supplant aspirin. Further, there are numerous examples of essential optically active amino acids which are important in human nutrition.
For many applications, the particular optically active amino acid that is required as a starting material must have an optical purity of at least about 65% and preferably at least about 90%. Such a purity level appears to be a requirement particularly in the case of optically active acyl amino acids. Also, for reasons of commercial practicality, a particular required optically active amino acid needs to be made from a starting precursor in a yield that is economical. For example, a yield of at least about 50% of an amino acid enantiomer appears to be desirable.
Previously, I have provided a method for preparing optically-active amino acid derivatives involving the contacting of a hydrolytically active lipase in a solvent with an oxazolone precursor; in particular, a 5(4H)-oxazolone (see pending Ser. No. 786,731). This method produces amino acids in substantial enantiomeric excess.
Although very useful, this method has a reaction rate and degree of enantioselectivity that vary depending on the C-4 substituents present in the precursor 5(4H)-oxazolones. It would be desirable to have an improved enzyme catalyzed synthetic process for directly producing any one of many natural and non-natural L-amino acids in high optical purity, in high yield, and at a useful reaction rate from such precursors.
The present invention provides such an improved process.